It has been illustrated in our laboratories that the Auger effect accompanying the decay of iodine-125 and bromine-77 is extremely toxic to cultured cells when these radionuclides are incorporated into DNA in the forms of 5-iodo-/5-bromo-2-deoxyuridine. Our studies with these and other Auger emitters (thallium-201, indium-111, technetium-99m, selenium-75, chromium-51) have also shown the ineffectiveness of this decay mode when it occurs at a distance from DNA. These studies emphasize the need for a systematic and comprehensive understanding of the role of the Auger effects in Radiation Biology. This will not only result in an accurate approximation of the dose delivered and therefore be highly informative in the fields of Helath Physics and Nuclear Medicine, but will also help in the development of a concrete strategy for the targeted radiotherapy of neoplastic disease using internal emitters. We now propose to further our investigations by using the established culture test system to study the radiotoxicity of different compounds, radiolabeled with various Auger emitters, that will localize within specific compartments inside the cell. The kinetics of uptake and intracellular microscopic distribution of these labeled compounds will be measured and their relationships to biological consequences determined. The relative sensitivities of various cell lines to Auger electrons and low LET radiations will be compared and the differences related to their variations in DNA content and ability to repair double and single-strand breaks. Cytogenetic changes, transformations, and mutagenesis will be scored in cell cultures exposed to Auger and alpha emitters and the results interpreted in relation to their lethal effects. An electron spin resonance study of 125IUdR 123IUdR, 77BrUdR, and 75Seguanosine will be initiated to elucidate the action of Auger electrons at the molecular level. This information will be used to establish the potential biohazards and/or therapeutic benefits fo these compounds. Lastly, the therapeutic efficacy of some of the compounds will be examined and compared with 125IUdR in the mouse ascites tumor model established in this laboratory.